Where Art Thou O treatment for diabetic neuropathy: the sequel

ABSTRACT

Introduction

Having lived through a pandemic and witnessed how regulatory approval processes can evolve rapidly; it is lamentable how we continue to rely on symptoms/signs and nerve conduction as primary endpoints for clinical trials in DPN.

Areas covered

Small (Aδ and C) fibers are key to the genesis of pain, regulate skin blood flow, and play an integral role in the development of diabetic foot ulceration but continue to be ignored. This article challenges the rationale for the FDA insisting on symptoms/signs and nerve conduction as primary endpoints for clinical trials in DPN.

Expert opinion

Quantitative sensory testing, intraepidermal nerve fiber density, and especially corneal confocal microscopy remain an after-thought, demoted at best to exploratory secondary endpoints in clinical trials of diabetic neuropathy. If pharma are to be given a fighting chance to secure approval for a new therapy for diabetic neuropathy, the FDA needs to reassess the evidence rather than rely on ‘opinion’ for the most suitable endpoint(s) in clinical trials of diabetic neuropathy.

KEYWORDS:

• Diabetic neuropathy
• nerve conduction studies
• skin biopsy
• corneal confocal microscopy
• clinical trials

Article highlights

• Diabetic neuropathy is a cause of much morbidity and increased mortality with debilitating neuropathic pain, sexual dysfunction, foot ulceration, and amputation.

• Screening for diabetic neuropathy with a monofilament is not fit for purpose as it only identifies patients at risk of foot ulceration with advanced nerve damage.

• Corneal confocal microscopy is a rapid noninvasive ophthalmic imaging technique that detects early sub-clinical neuropathy and could easily be deployed alongside retinal screening.

• Current FDA endpoints for clinical trials in diabetic neuropathy are not fit for purpose and as a consequence we have no approved disease modifying therapies for diabetic neuropathy.

• Evidence rather than opinion, supports the use of corneal confocal microscopy as a primary endpoint to identify early nerve regeneration and provide a go/no-go signal for longer term trials utilizing symptoms and signs of diabetic neuropathy.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer Disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This manuscript was not funded.